Assessment of solubility and intestinal absorption in vitro of praziquantel in solid dispersions of polyethylene glycol 6000

The aim of this study was to investigate the impact of solid dispersions of polyethylene glycol 6000 (PEG 6000), using the co-precipitation method, on the in vitro solubility and intestinal absorption of praziquantel (PZQ). The solubility of PZQ in solid dispersions and physical mixtures was assessed in purified water and TC-199 buffer. The everted intestinal sac model was employed to assess, in vitro, intestinal absorption of PZQ. A significant enhancement in both in vitro solubility and intestinal absorption of PZQ was found in solid dispersions compared to pure PZQ and physical mixtures. This positive series of preliminary results showed that solid dispersion of PEG 6000 is a valuable strategy for increasing bioavailability of PZQ and could also prove useful for other poorly water-soluble drugs.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Mitigation of the Negative Impact of Warming on the Coffee Crop: The Role of Increased Air [CO2] and Management Strategies

Crop sustainability can be threatened by new environmental challenges regarding predicted climate changes and global warming. Therefore, the study of real biological impacts of future environmental conditions (e.g., increased air [CO2], supra-optimal temperature and water scarcity) on crop plants, as well as the re-evaluation of management procedures and strategies, must be undertaken in order to improve crop adaptation and promote mitigation of negative environmental impacts, thus affording crop resilience. Coffee is a tropical crop that is grown in more than 80 countries, making it one of the world’s most traded agricultural products, while involving millions of people worldwide in the whole chain of value. It has been argued that this crop will be highly affected by climate changes, resulting in decreases in both suitable areas for cultivation and productivity, as well as impaired beverage quality in the near future. Here, we report recent findings regarding coffee species exposure to combined supra-optimal air temperatures and enhanced air [CO2], and impacts of drought stress on the crop. Ultimately, we discuss key strategies to improve coffee performance in the context of new environmental scenarios. The recent findings clearly show that high [CO2] has a positive impact on coffee plants, increasing their tolerance to high temperatures. This has been related to a better plant vigor, to the triggering of protective mechanisms, and to a higher functional status of the photosynthetic machinery. Even so, coffee plant is expected to suffer from water scarcity in a changing world. Therefore, discussion is focused on some important management strategies (e.g., shade systems, crop management and soil covering and terracing), which can be implemented to improve coffee performance and sustain coffee production in a continually changing environment

High-resolution shotgun proteomics reveals that increased air [CO2] amplifies the acclimation response of coffea species to drought regarding antioxidative, energy, sugar, and lipid dynamics

Funding Information: This work received funding support from the European Union's Horizon 2020 research and innovation program (grant agreement No 727934 , project BreedCAFS), and from national funds from Fundação para a Ciência e a Tecnologia, I.P. (FCT) , Portugal, through the project PTDC/ASP-AGR/31257/2017 , and the research units UIDB/00239/2020 ( CEF ), and UIDP/04035/2020 (GeoBioTec) and under the Scientific Employment Stimulus - Individual Call (CEEC Individual) - 2021.01107.CEECIND/CP1689/CT0001 (IM) . Fellowships from the Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil (CNPq) , (to F.M. DaMatta and F.L. Partelli), and Fundação de Amparo à Pesquisa do Estado de Minas Gerais, Brazil (FAPEMIG, projects CRA-RED-00053-16 and APQ 01512-18 , to F.M. DaMatta) are also greatly acknowledged. Publisher Copyright: © 2022 Elsevier GmbHAs drought threatens crop productivity it is crucial to characterize the defense mechanisms against water deficit and unveil their interaction with the expected rise in the air [CO2]. For that, plants of Coffea canephora cv. Conilon Clone 153 (CL153) and C. arabica cv. Icatu grown under 380 (aCO2) or 700 μL L−1 (eCO2) were exposed to moderate (MWD) and severe (SWD) water deficits. Responses were characterized through the activity and/or abundance of a selected set of proteins associated with antioxidative (e.g., Violaxanthin de-epoxidase, Superoxide dismutase, Ascorbate peroxidases, Monodehydroascorbate reductase), energy/sugar (e.g., Ferredoxin-NADP reductase, NADP-dependent glyceraldehyde-3-phosphate dehydrogenase, sucrose synthase, mannose-6-phosphate isomerase, Enolase), and lipid (Lineolate 13S-lipoxygenase) processes, as well as with other antioxidative (ascorbate) and protective (HSP70) molecules. MWD caused small changes in both genotypes regardless of [CO2] level while under the single imposition to SWD, only Icatu showed a global reinforcement of most studied proteins supporting its tolerance to drought. eCO2 alone did not promote remarkable changes but strengthened a robust multi-response under SWD, even supporting the reversion of impacts already observed by CL153 at aCO2. In the context of climate changes where water constraints and [CO2] levels are expected to increase, these results highlight why eCO2 might have an important role in improving drought tolerance in Coffea species.publishersversionpublishe

Lipid profile adjustments may contribute to warming acclimation and to heat impact mitigation by elevated [CO2] in Coffea spp

This work was supported by European Union, Program Horizon 2020, call H2020-SFS-2016-2, action RIA, and Portuguese national funds from Fundacao para a Ciencia e a Tecnologia (project PTDC/ASP-AGR/31257/2017; Funding from CNPq (fellowships to E. Campostrini, F.L. Partelli, and F.M. DaMatta) is also acknowledged.An unexpected heat resilience, and the mitigation of heat impacts by elevated [CO2] were recently reported in Coffea spp. Plants must maintain membrane fluidity and integrity to cope with temperature changes, which requires an adequate lipid dynamics. This work provides the lipid profile (galactolipids, GL; phospholipids, PL; sulfolipids, SL) of chloroplast membranes, and the expression of a set of genes related to lipid metabolism in Coffea arabica L. (cv. Icatu and IPR108) and C. canephora cv. Conilon CL153, under elevated [CO2] (380 or 700 μL L−1), heat (25/20, 31/25, 37/30 and 42/34 °C, day/night) and their interaction. Major membrane lipids alterations, different among genotypes, included: A) responsiveness of total fatty acids (TFAs) synthesis to [CO2] (except IPR108) and heat (except CL153); stronger remodeling (unsaturation degree) in the 700-plants from 37/30 °C to 42/34 °C, coordinated at transcriptional level with the down-regulation of fatty acid desaturase FAD3 gene (C. arabica) and up-regulation of lipoxygenase genes LOX5A (CL153 and Icatu) and LOX5B (Icatu) at the highest temperature; B) quantitative and qualitative modifications in GL (monogalactosyldiacylglycerol, MGDG; digalactosyldiacylglycerol, DGDG), PL (phosphatidylcholine, PC; phosphatidylglycerol, PG), and SL (sulfoquinovosyldiacylglycerol, SQDG) classes, prompted by heat, elevated [CO2], and, especially, the interaction, in CL153 and Icatu. Overall membrane enrichment with MGDG and DGDG as a result of heat and [CO2] interaction in these genotypes, but at the highest temperature only in Icatu the high [CO2] maintained greater contents and unsaturation values of these GLs than in the 380-plants. C) Among PL classes, PG seems to play an active role in heat acclimation of C. arabica genotypes, increasing in 700-plants at 42/34 °C. Globally, Icatu often showed changes closer to those of heat tolerant cv. CL153 than to cv. IPR108. Overall, lipid profile adjustments in chloroplast membranes, from TFAs bulk until FA unsaturation within each class, are expected to contribute to long-term acclimation to climate changes in coffee plant.publishersversionpublishe

Eritema necrolítico migratório associado à síndrome glucagonoma: descrição de um caso

Necrolytic migratory erythema is a rare skin condition that consists of migrating areas of erythema with blisters that heal with hyperpigmentation. It usually occurs in patients with an alpha islet cell tumor of the pancreas-or glucagonoma-and when associated with glucose intolerance, anemia, hyperglucagonemia, and weight loss defines the glucagonoma syndrome. We describe a 52-year-old female patient with necrolytic migratory erythema associated with glucagonoma syndrome who had metastatic disease at presentation and passed away one week after her admission. The autopsy showed a tumor in the body of the pancreas, which was diagnosed as a neuroendocrine tumor and confirmed by immunohistochemistry. The diagnosis of necrolytic migratory erythema is a matter of great importance, since it might be an auxiliary tool for the early detection of glucagonoma.O eritema necrolítico migratório é uma rara condição cutânea que se apresenta como lesões eritematosas, migratórias, com vesículas e bolhas na superfície, evoluindo para cura com hiperpigmentação. É freqüentemente observado em doentes com tumor de células alfa do pâncreas, ou glucagonoma, e quando associado com intolerância a glicose, anemia, hiperglucagonemia, e perda de peso definem a síndrome do glucagonoma. É descrito o caso de uma paciente do sexo feminino, 52 anos, branca, com eritema necrolítico migratório associado à síndrome do glucagonoma com doença metastática na apresentação, vindo a falecer uma semana após sua admissão. A autópsia mostrou um tumor no corpo do pâncreas diagnosticado como tumor neuroendócrino e confirmado pela imuno-histoquímica. O reconhecimento do eritema necrolítico migratório é de grande importância para a possibilidade de diagnóstico precoce do glucagonoma

New formulation of an old drug in hypertension treatment: the sustained release of captopril from cyclodextrin nanoparticles

Captopril (CAP) was the first angiotensin I-converting enzyme (ACE) inhibitor to be developed and is widely used in hypertension treatment. On the other hand, cyclodextrins (CDs) are cyclic oligosaccharides whose cone-shaped cavity allows formation of noncovalent inclusion complexes with appropriately sized guest molecules, thus modifying guest physical, chemical, and biological properties. Herein, the physicochemical characterization and in vivo ACE inhibition evaluation of seven CAP/CD complexes are reported. The inclusion complexes were prepared by spray-drying, freeze-drying, kneading, or lyophilization methods and characterized by nuclear magnetic resonance, Fourier-transformed infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy techniques. In vivo assays compared CAP and CAP/CD complex administration (0.5 mg kg−1 or 0.09 mg kg−1, n = 4–7) to evaluate the ACE inhibition by continuous infusion of angiotensin I (30 ng 50 μL−1 min−1) in conscious Wistar rats. The physicochemical analysis demonstrated complete amorphization and complexation between CAP and CDs, indicating the substitution of water molecules inside the CD cavity with CAP. During the infusion of angiotensin I, the administration of all CAP/CD complexes induced a reduction in mean arterial pressure similar to that observed upon CAP administration. The nanoparticles obtained by the kneading method (CAP/α-CD:KM) showed a potent and long-lasting inhibitory activity (∼22 hours) on the angiotensin I pressor effect. The results suggest that the inclusion complex of CAP and α-CD can function as a novel antihypertensive formulation that may improve therapeutic use of CAP by reducing its oral dose administration to once per day, thus providing better quality of life for almost 25% of the world’s population who suffer from hypertension

Biodiversidade, população e economia: uma região de mata atlântica [Biodiversity, Population, and Economy: a region of atlantic forest]

Minas Gerais; Rio Doce; mata atlântica; atlantic forest; sustainable development; conservation; regional development; environment

THE SUSCEPTIBILITY OF RECENT ISOLATES OF Schistosoma mansoni TO PRAZIQUANTEL

Introduction: Schistosomiasis is a chronic disease caused by trematode flatworms of the genus Schistosoma and its control is dependent on a single drug, praziquantel (PZQ), but concerns over PZQ resistance have renewed interest in evaluating the in vitro susceptibility of recent isolates of Schistosoma mansoni to PZQ in comparison with well-established strains in the laboratory. Material and methods: The in vitro activity of PZQ (6.5-0.003 µg/mL) was evaluated in terms of mortality, reduced motor activity and ultrastructural alterations against S. mansoni. Results: After 3 h of incubation, PZQ, at 6.5 µg/mL, caused 100% mortality of all adult worms in the three types of recent isolates, while PZQ was inactive at concentrations of 0.08-0.003 µg/mL after 3 h of incubation. The results show that the SLM and Sotave isolates basically presented the same pattern of susceptibility, differing only in the concentration of 6.5 µg/mL, where deaths occurred from the range of 1.5 h in Sotave and just in the 3 h range of SLM. Additionally, this article presents ultrastructural evidence of rapid severe PZQ-induced surface membrane damage in S. mansoni after treatment with the drug, such as disintegration, sloughing, and erosion of the surface. Conclusion: According to these results, PZQ is very effective to induce tegument destruction of recent isolates of S. mansoni

Hemoglobinopatias no Distrito Federal, Brasil

Em uma amostra de 3137 pessoas, residentes no Distrito Federal, foram detectadas as seguintes hemoglobinas: em 3009(95,92%) HbAA; em 91 (2,90%) HbAS; em 20(0,64%) HbAC; em 8 (0,26%) talassemia beta minor; em 5(0,16%) HbAJ alfa; em 3 (0,09%) HbAM e em 1 (0,03%) talassemia major associada com HbAS. A HbAS têm as seguintes freqüências, quanto ao grupo racial: branco - 1,84%; mulato claro 2,55%; mulato médio-3,68%; mulato escuro - 6,80%; negro -10,43% e mestiço de índio -3,85%.The hemoglobins of 3137 persons from the Federal District, Brazil was studied. The identified types of hemoglobins were: HbAA (3009 - 95,92%); HbAS (91 - 2,90%); HbAC (20 - 0,64%) beta thalassemia minor (8 - 0,26%); HbAJ alpha (5 - 0,16%); HbAM (3 - 0,09%) and beta thalassemia major/HbS (1 - 0,03%). The frequencies of sickle cell trait (HbAS) of each racial class were: white (1,84%); light mulatto (2,55%); medium mulatto (3,68%); dark mulatto(6,80%), negro (10,43%)and indian mestizo (3,85%)

Ferromagnetic Levan Composite: An Affinity Matrix to Purify Lectin

A simple and inexpensive procedure used magnetite and levan to synthesize a composite recovered by a magnetic field. Lectins from Canavalia ensiformis (Con A) and Cratylia mollis (Cramoll 1 and Cramoll 1, 4) did bind specifically to composite. The magnetic property of derivative favored washing out contaminating proteins and recovery of pure lectins with glucose elution. Cramoll 1 was purified by this affinity binding procedure in two steps instead of a previous three-step protocol with ammonium sulfate fractionation, affinity chromatography on Sephadex G-75, and ion exchange chromatography through a CM-cellulose column